IQCA-TASS: a nano-scaled P-selectin inhibitor capable of targeting thrombus and releasing IQCA/TARGD(S)S in vivo

• DOI: 10.1039/c6tb02705a
• Publication Date: 2016-12-15T18:23:32Z
• Authors: Jianhui Wu; Haimei Zhu; Ming Zhao; Yuji Wang; Guodong Yang; Yaonan Wang; Shurui Zhao; Lin Gui; Xiaoyi Zhang; Shiqi Peng
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

Thrombosis is a serious threat to human health worldwide. Tetrahydroisoquinoline-3-carboxylic acid (IQCA) an antithrombotic agent, while Thr-Ala-Arg-Gly-Asp(Ser)-Ser (TASS) can target thrombus. Herein, tetrahydro-isoquinoline-3-carbonyl-Thr-Ala-Arg-Gly-Asp(Ser)-Ser (IQCA-TASS) was designed with the aim towards discovery of nano-delivery system for targeting In vitro, IQCA-TASS acted on P-selectin and down-regulated expression. The IC50 values against platelet aggregation induced by four aggregators were less than 0.45 nM. vivo, targeted thrombus, released IQCA TASS inside showed dose-dependent anti-thrombotic action, which minimal effective dose 1 nmol kg-1, anti-inflammatory action. Even up μmol 1000 times dose, still no toxic reaction. rat plasma, formed nanoparticles diameters 41 nm. interactions both resting activated platelets imaged. should be safe nano-medicine capable thrombus releasing anti-thrombotic/anti-inflammatory pharmacophores in disease sites.